The mouse hematopoietic cell line, 32D, was transfected with c-fms, which encode for the CSF-1 receptor, a tyrosine kinase (TK) . In the absence of CSF-1, transfected cells show moderate levels of arachidonic acid (A.A.) release and produce a substantial amount of prostaglandin E2 (PGE2) in comparison with the original cell line. Exposure of transfected cells to CSF-1, while inducing a substantial increase in arachidonate release, nevertheless resulted in inhibition of PGE2 production. Addition of ST638, a tyrosine kinase inhibitor, to cells transfected with c-fms in the absence of CSF-1 inhibited PGE2, production within 10 to 60 minutes. Its addition to the same cells in the presence of CSF-1 induced an opposite effect, but required longer treatment (24 hours). In either cell type, A.A. release was not affected by this agent. These data indicate that CSF-1 receptor may regulate cyclooxygenase activity. The different effect of CSF-1 receptor on PGE, production in the presence or absence of CSF-I and the opposite effect of a tyrosine kinase inhibitor on PGE2 suggest that both the receptor alone or the receptor-ligand complex transduce an active, but different, signal through tyrosine phosphorylation.